title: Genetic deletion of IL-17A reduces cigarette smoke-induced inflammation and alveolar type II cell apoptosis.
abstract: Chronic obstructive pulmonary disease (COPD) is an inflammatory disorder marked by relative resistance to steroids. Inflammation and apoptosis have been suggested to be important mechanisms for COPD. Interleukin (IL)-17 superfamily has been associated with chronic inflammation and diminished responses to steroids. It is reasonable to consider that IL-17 may play a role in the pathogenesis of COPD. In this study, we examined IL-17 expression in mice exposed to cigarette smoke (CS) and investigated the contribution of IL-17 to CS-induced inflammation and alveolar cell apoptosis in IL-17(-/-) mice. After exposing wild-type and IL-17(-/-) mice to mainstream CS for 4 wk, IL-17A, but not IL-17F, expression was increased in mice upon CS exposure. Neutrophil infiltration in the lungs of IL-17(-/-) mice was significantly decreased. In IL-17(-/-) mice, there is reduced expression of IL-6, macrophage inflammatory protein-2, and matrix metalloproteinase-12 compared with wild-type mice after CS exposure. The number of apoptotic type II alveolar cells was significantly increased in CS-exposed wild-type mice but not in IL-17(-/-) mice. The effect of IL-17A on type II alveolar cell apoptosis was confirmed in vitro through either addition of IL-17A or transient knockdown of IL-17A by small-interfering RNA transfection in type II alveolar cells. These findings suggest that IL-17A plays an important role in the inflammatory response to CS exposure through increased multiple inflammatory mediators. Moreover, IL-17 may also contribute to type II alveolar cell apoptosis. This study opens a new option in targeting IL-17A to modulate inflammatory response to CS and may be the bases for new therapy for COPD.
authors.affiliation: Meakins-Christie Laboratories and Respiratory Division, Dept. of Medicine McGill Univ., 3626 rue St. Urbain, Montreal, QC, Canada H2X 2P2. qutayba.hamid@mcgill.ca.
authors.forename: Ying
authors.initials: Y
authors.lastname: Chang
authors.forename: Laila
authors.initials: L
authors.lastname: Al-Alwan
authors.forename: Severine
authors.initials: S
authors.lastname: Audusseau
authors.forename: Fazila
authors.initials: F
authors.lastname: Chouiali
authors.forename: Juna
authors.initials: J
authors.lastname: Carlevaro-Fita
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Iwakura
authors.forename: Carolyn J
authors.initials: CJ
authors.lastname: Baglole
authors.forename: David H
authors.initials: DH
authors.lastname: Eidelman
authors.forename: Qutayba
authors.initials: Q
authors.lastname: Hamid
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002478:Cells, Cultured; D054426:Chemokine CXCL2 / Q000276:immunology / Q000378:metabolism; D005260:Female; D020381:Interleukin-17 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D053508:Matrix Metalloproteinase 12 / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000166:cytology / Q000276:immunology; D011014:Pneumonia / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D020545:Respiratory Mucosa / Q000166:cytology; D012907:Smoking / Q000009:adverse effects* / Q000276:immunology*
chemical_list: D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; C098680:Il17a protein, mouse; D020381:Interleukin-17; D015850:Interleukin-6; D053508:Matrix Metalloproteinase 12
keywords: chronic obstructive pulmonary disease; interleukin-17